This project has the following objectives: 1. To understand the heterogeneous pathogenesis of the syndromes of isolated gonadotropin deficiency (IGD), i.e., bihormonal (FSH and LH deficiency) and unihormonal (FSH) deficiency; 2. To increase the utility of assays for the alpha chain of glycoprotein hormones and to develop assays for the unique beta-chains of TSH, FSH, and LH; 3. To examine further the clinical and immunologic status of an unique patient with isolated FSH deficiency who has developed persistent human anti-hFSH antibodies; 4. To evaluate the roles of luteinizing hormone releasing factor (LRF) and of human prolactin (hPRL) in the control of gonadotropin and subunit release in normal man and in IGD, and its modification by physiologic and pharmacologic agents; 5. To examine the responsiveness of the gonad to short-term and long-term clomiphene and gonadotropin therapy, and to develop methods to distinguish between constitutional delay of puberty and IGD; 5. To examine the responsiveness of the gonad to short-term and long-term clomiphene and gonadotropin therapy, and to develop methods to distinguish between constitutional delay of puberty and IGD; 6. To understand the nature of the lack of gonadal responsiveness to endogenous and exogenous gonadotropins in the syndrome of amenorrhoea, hypergonadotropism and apparently normal ovarian follicular apparatus. Specifically, the possible role of antibody to circulating gonadotropin and/or antibody to gonadotropin receptors in the gonad. And to extend these studies to patients with premature ovarian failure.